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2012-05
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/133843

Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson's disease

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Induced pluripotent stem cells (iPSC) offer an unprecedented opportunity to model human disease in relevant cell types, but it is unclear whether they could successfully model age-related diseases such as Parkinson's disease (PD). Here, we generated iPSC lines from seven patients with idiopathic PD (ID-PD), four patients with familial PD associated to the G2019S mutation in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene (LRRK2-PD) and four age- and sex-matched healthy individuals (Ctrl). Over long-time culture, dopaminergic neurons (DAn) differentiated from either ID-PD- or LRRK2-PD-iPSC showed morphological alterations, including reduced numbers of neurites and neurite arborization, as well as accumulation of autophagic vacuoles, which were not evident in DAn differentiated from Ctrl-iPSC. Further induction of autophagy and/or inhibition of lysosomal proteolysis greatly exacerbated the DAn morphological alterations, indicating autophagic compromise in DAn from ID-PD- and LRRK2-PD-iPSC, which we demonstrate occurs at the level of autophagosome clearance. Our study provides an iPSC-based in vitro model that captures the patients' genetic complexity and allows investigation of the pathogenesis of both sporadic and familial PD cases in a disease-relevant cell type.

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Matèries

Dopamina, Metabolisme, Fenotip, Genètica, Neurones, Malaltia de Parkinson, Patologia, Cèl·lules mare

Matèries (anglès)

Dopamine, Metabolism, Phenotype, Genetics, Neurons, Parkinson's disease, Pathology, Stem cells

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Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Patologia i Terapèutica Experimental)

Citació

SÁNCHEZ DANÉS, Adriana, RICHAUD-PATIN, Yvonne, CARBALLO CARBAJAL, Iria, JIMÉNEZ DELGADO, Senda, CAIG, Carles, MORA, Sergio, DI GUGLIELMO, Claudia, EZQUERRA TRABALÓN, Mario, PATEL, Bindiben, GIRALT TORROELLA, Albert, CANALS I COLL, Josep m., MEMO, Maurizio, ALBERCH I VIÉ, Jordi, LÓPEZ BARNEO, José, VILA FARRÉ, Miquel, CUERVO, Ana maria, TOLOSA, Eduardo, CONSIGLIO, Antonella, RAYA CHAMORRO, Ángel. Disease-specific phenotypes in dopamine neurons from human iPS-based models of genetic and sporadic Parkinson's disease. _EMBO Molecular Medicine_. 2012. Vol. 4, núm. 5, pàgs. 380-395. [consulta: 10 de desembre de 2025]. ISSN: 1757-4676. [Disponible a: https://hdl.handle.net/2445/133843]

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